The separation of enantiomers is considered to be one of the more difficult tasks faced by practitioners of analytical chemistry. Chiral separations are one of the most challenging types of purification because of the extreme similarity between the two components in a racemic mixture. Each component is a mirror image of the other. These chiral components exhibit identical physical properties in non-chiral environments. As a result, conventional separation technology such as gas chromatography, liquid chromatography and capillary electrophoresis have been modified to provide a chiral environment.
Different approaches to providing a chiral environment have been attempted. Chiral stationary phases have been developed. These are chromatography columns with chiral functional groups that interact with the analytes. Additives can be added to a mobile phase creating a mobile phase that has chiral selectivity. Sometimes these chiral stationary phases are used in conjunction with a chiral mobile phase with mixed results. One problem with such an approach is the instability of the column. Additionally, commercial additives can be cost-prohibitive, especially at the analytical scale.
Chiral separations have been accomplished using a variety of techniques. Over the last thirty years investigators have shown that chiral separations are possible using gas chromatography (GC), liquid chromatography (LC), gel electrophoresis, paper electrophoresis, and capillary electrophoresis (CE). These separations are based on the ability of the enantiomers of the sample to differentially interact with a chiral phase that is part of the separation system.
The chiral phase can be embodied in a variety of ways. In chromatography, the chiral phase is conventionally part of the stationary phase, or column. In both GC and LC, a wide variety of chiral columns are available. The adsorption of the enantiomers by the stationary phase is the sum of both achiral and chiral interactions. The achiral interactions might include ionic, hydrogen bonding, and hydrophobic adsorption. The chiral interactions are derived from the spatial relationship of the achiral interactions. The energy difference contributed by this chiral interaction is the basis for the chiral separation.
The efficiency of the current generation of chiral chromatographic systems is generally low, thus the difference in the free energy of the interaction between the chiral modifier and the enantiomers must be relatively large in order to gain adequate resolution. This large energy difference requirement contributes to the low efficiency of many chiral HPLC systems (5000 to 10000 plates), and the tailing peaks observed on many chiral columns. This large energy difference requirement also prevents chiral HPLC columns from being of general use. Currently, chiral HPLC columns are selective for small classes of compounds, so more than fifty chiral phases have been commercialized. In this environment, method development is highly empirical and very tedious. There is a need to create systems which separate larger classes of enantiomers or provide easier method development.
Currently, there exists a need to develop cost-effective chiral mobile phases that can effectively facilitate the separation of enantiomers. Optimally, these mobile phases comprise chiral solvents and not merely additives.